tbuckley/cabot-search huggingface dataset:
Abstract 14519: End Stage Heart Failure Patients With Do-Not-Resuscitate Code Status Have Dramatically Reduced Hospitalization Cost and Length of Stay
Authors: Abdelrahman Masri, Ayesha Abbasi, Sami Shoura, Muhammad Usman Almani, Mukunthan Murthi, Abdallah Masri
Journal: Circulation (2022)

Introduction: End-stage CHF (ES-CHF) poses a significant burden on healthcare system, DNR orders are often associated with comfort care measures, decreased pain and suffering, as well as healthcare resource utilization (cost and LOS). Objective: To quantify the discrepancy in cost and LOS between ES-CHF patients with DNR orders versus without DNR code status. Methodology: Nationwide Inpatient Sample (NIS) database years 2017-2018 was invoked for hospitalizations with primary or secondary diagnosis of ES-CHF, DNR status, comorbidities, and hospitalization outcome using ICD-10 codes. Characteristics of ES-CHF hospitalization with DNR versus no DNR code status were compared. Because of the nature of NIS database, timing of diagnoses and DNR code status could not be established, thus regression analysis for predictors of hospital charges, cost, and LOS was not feasible. Regression analyses were performed to explore predictors of mortality. Stata/MP 16.0 software was used. Results: 40,655 adult hospitalization had the diagnosis of ES-CHF in years 2017-2018 in the United States, among them, 12,300 (30%) had DNR code status, 35% were females, 83% of patients had &gt;=3 comorbid conditions (Charlson comorbidity index&gt;=3). Overall inpatient mortality rate was 12% (25% vs 7% in DNR vs no DNR group, respectively, p&lt;0.001), mean LOS was 10+-15 days (8 vs 11 days in DNR vs no DNR group, respectively, p&lt;0.001), mean total hospital charges was $159,122+-358,186 ($79,434 vs $193,873 in DNR vs no DNR group, respectively, p&lt;0.001). Significantly higher rates of CABG history, atrial fibrillation, COPD, peripheral vascular disease, hypothyroidism, CKD, liver disease, electrolyte disturbances, AKI, and sepsis were found among DNR group. In all patients with ES-CHF, independent predictors of inpatient mortality included older age, DNR status, history of CABG, peripheral vascular disease, liver disease, electrolyte disturbances, smoking, AKI, and sepsis. Conclusion: The presence of DNR code status in ES-CHF patients admitted to the hospital for any was associated with had dramatically reduced hospital charges and cost by more than the half, and with significantly shorter LOS.
Abstract 15422: Trend of Stroke in Mechanical Circulatory Support Devices: Insight From the National Inpatient Sample Database
Authors: Harigopal Sandhyavenu, Amro Taha, Irisha Badu, Sindhura Ananthaneni, Mohammed Faisaluddin, Waqas Ullah
Journal: Circulation (2022)

Background: Mechanical circulatory support (MCS) is increasingly being used as a bridge or destination therapy in advanced heart failure. Data on the risk of complications including stroke are limited. Methods: The National Inpatient Database (NIS) from 2002-2019 was analyzed to identify patients with stroke and classified based on MCS use into MCS and no-MCS groups. Using a linear regression model, trends of stroke were obtained. Result: On trend analysis, there was a steep increase in the incidence of stroke from 2002-2013 (MCS: 21% to 41% and no-MCS: 20% to 36%) with a decline in the trend by 2019 in MCS group compared to no-MCS group (38% vs. 44%). Annual trends of stroke in impella, extracorporeal membrane oxygenation (ECMO), intra-aortic balloon pump (IABP) and left ventricular assist device (LVAD) had initial increasing trends from 2002-2013 (1% to 18%, 2.5% to 40%, 24% to 44% and 14% to 40% respectively). Patients on LVAD had a plateaued rate from 2014-2019 (40% to 46%) while the rate in impella and ECMO continued to increase exponentially from 2014-2019 (18% to 81% and 40% to 58% respectively). Conversely, there has been a decline in the trend in IABP by 2019 (32%). Conclusion: The risk of stroke in patients with the use of mechanical circulatory support devices increased exponentially until 2013 and has shown a declining trend thereafter.
Abstract 15460: Comprehensive Diet and Exercise Intervention During Radiation Therapy Can Improve Metabolic and Inflammatory Markers in Breast Cancer Patients
Authors: Gopika Senthilkumar, Aronne M Schottstaedt, Melinda Stolley, Christopher Chitambar, Alexis Visotcky, Anjishnu Banerjee, John Longo, Tracy Kelly, Adam Currey, Carmen Bergom
Journal: Circulation (2022)

While radiation therapy (RT) is effective for reducing cancer burden in breast cancer (BC) patients, its side effects promote sedentary behavior and accumulation of adipose mass. Obesity and inactivity further increase the risk for cardiovascular co-morbidities and mortality. To combat these effects, we piloted a 12-week Stay on Track (SOT) exercise and diet intervention for breast cancer patients during their RT. We hypothesize that SOT will positively influence body composition and metabolic and inflammatory biomarkers in BC patients. A prospective, randomized control trial for patients with non-metastatic BC undergoing whole-breast RT was conducted. The intervention ( A; 21 patients) group participated in 3 personal excercise training sessions, 3 dietary counseling sessions, and received 3 text message reminders per week to adhere to lifestyle recommendations. The control (B; 22 patients ) group received an informative binder. All patients received a Fitbit, and at baseline, 3months, and 6months, measurements of blood biomarkers and dual-energy x-ray absorptiometry (DXA) scans were conducted. A mixed models analysis with a significance value of 0.05 was conducted, and estimated change from baseline with SE’s are reported. There was trend towards lower BMI (-0.95, 0.49; p=0.06) at 6mo and decreased visceral fat (-2.17, 1.22; p=0.081) at 3mo in A only. B had an increase in HbA1C at 3mo compared to baseline (0.26, 0.10; p=0.01) which stayed elevated at 6mo (0.22, 0.13; p=0.08). B also had an increase in glucose levels at 6mo (8.42, 3.94; p=0.04), with a trend towards a decrease in insulin (-14.30, 9.85; p=0.15). A had no changes in these levels. There was a significant decrease in leptin levels at 6mo in B only (-13583.7, 6184.2, p=0.03). Adiponectin levels trended higher in A compared to B at 6mo (3143.42, 2265.1; p=0.17). Analysis of inflammatory cytokines showed a decrease in anti-inflammatory IL-1R-a in B (-3.46, 1.24; p=0.01), and a reduction in pro-inflammatory IL-8 levels in A (-2.77, 1.15; p=0.02). We conclude that SOT may positively influence body composition and metabolic and inflammatory biomarkers in BC patients. Targeted lifestyle interventions during RT are feasible and could help decrease cardiovascular co-morbidities in BC.
Abstract 15355: Evaluating the Electrocardiographic Characteristics of Transgender Patients Undergoing Gender-Affirming Hormone Therapy With Artificial Intelligence
Authors: Philip Sang, Fadi Adel, Arvind Maheshwari, Kathryn Mangold, Zachi Attia, Paige Cummings, Caroline Davidge-Pitts, Francisco Lopez-Jimenez, Paul Friedman, Peter A Noseworthy, Rekha Mankad
Journal: Circulation (2022)

Evaluating the Electrocardiographic Characteristics of Transgender Patients Undergoing Gender-affirming Hormone Therapy with Artificial Intelligence Introduction: An artificial intelligence (AI) electrocardiogram (ECG) algorithm has been demonstrated to identify a patient’s birth designated sex with 90.4% accuracy with an AUC = 0.97. However, the algorithm has not been evaluated in transgender and gender diverse individuals. We aimed to determine how the algorithm output varies among transgender individuals seen at the Mayo Clinic Transgender and Intersex Specialty Care Clinic (TISCC) who are undergoing gender-affirming hormonal treatment (GAHT). Methods: We applied the algorithm (which assessed the probability of “male” between 0 and 1, with &lt; 0.5 considered as “female” and &gt; 0.5 as “male”) to ECGs obtained from patients in the TISCC before and after the initiation of GAHT. GAHT frequently involves the use of testosterone in transgender men, and estrogen and anti-androgen agents in transgender women. Patient characteristics, including the date of the initiation of GAHT, were collected through chart review. Results: Among transgender women, the AI model probability of “male” decreased from 0.84± 0.25 (12/86 classified as males) to 0.59±0.36 (68/173 classified as male) with GAHT (p &lt; 7.8e-10). Among transgender men, the AI model probability of “male” increased from 0.16 ± 0.28 (7/47 classified as male) to 0.41 ±0.38 (22/53 classified as male) with GAHT (p &lt; 2.4e-4). Conclusion: After GAHT initiation, the Mayo Clinic AI ECG algorithm assigns a higher probability of being male among transgender men and a lower probability of being male among transgender women. These findings warrant further investigation into the electrocardiographic differences across genders and the effects of GAHT on the human heart.
Abstract 14685: Predictors of Prognosis in Cardiogenic Shock Complicating Initially Acute Myocardial Infarction
Authors: Tamilla Muzafarova, Zuzana J Motovska, Ota HLINOMAZ, Petr Kala, Milan Hromadka, Jan Precek, Jan Mrozek, Jan Matejka, Jiri Kettner, Josef Bis, Jiri Jarkovsky
Journal: Circulation (2022)

Introduction: Despite modern treatment methods, cardiogenic shock mortality complicates acute myocardial infarction (CS-AMI) remains high. Hypothesis: The study of factors affecting CS-AMI outcomes is essential. Methods: Data from the all-comers' National Registry of Coronary Interventions from 2016 to 2020 were evaluated. Of 50,745 patients with AMI (STEMI/NSTEMI) 2,822 patients (5.6%) had initially CS (72.6% men, mean age 67.6 (12) yrs). The study analyzed the predictive value of such traditional cardiovascular risk factors related to the MI (sex, age, previous PCI or CABG, renal failure, localization of MI, time delay to reperfusion), comorbidities (expressed by the Deyo modification of Charlson comorbidity index), the severity of the condition on admission (mechanical ventilation, resuscitation), the extent of coronary artery disease and procedural success (the number of affected vessels, TIMI flow before and after PCI, LM disease), and such untraditional factors as season, weekday and day time. Multivariable analysis was used to identify independent predictors of prognosis in patients with CS-AMI. Results: The 30days mortality was 50.7%. As independent predictors of prognosis were identified age (older 80yrs, OR 4.97;95% CI 3.73-6.61), resuscitation (1.34; 1.07-1.67), mechanical ventilation (1.39;1.10-1.75), 3-vessel disease 1.39;1.12-1.72), left main disease (1.26; 1.01-1.57), and post-procedural TIMI flow lower 3 (1.14; 0.79-1.66). The independent predictive value of the comorbidity index was not confirmed (1.062;0.796-1.417). The numerically higher mortality rate was shown during a) autumn time (54.2%) and winter (51.8%), b) weekend (51.45%) (vs. working week (50.03%)), c) working hours (49.3%) (vs. the after-working hours (47.6%)). The multivariate analysis did not confirm the independent predictive value of these variables. Conclusions: Mortality of CS-AMI patients is significantly and independently influenced by factors confounding their circulatory instability, such as resuscitation and respiratory failure, the extent of coronary disease, and the success of reperfusion therapy. The independent impact of comorbidity and non-traditional factors on the prognosis of these patients has not been confirmed.
Abstract 14720: Marked Increase in Mitochondria Degradation in Engineered Heart Tissue During Reperfusion
Authors: Mireia Nager, Zambarlal Bhujabal, Kenneth B Bowitz Larsen, Trine B Kalstad, Truls Myrmel, Asa B Birgisdottir
Journal: Circulation (2022)

Introduction: Engineered heart tissue (EHT) consisting of beating cardiomyocytes differentiated from human inducible pluripotent stem cells (hiPSCs) has the potential to recapitulate molecular and functional features of the human heart. Cardiac homeostasis is dependent on lysosomal removal of damaged mitochondria through selective autophagy (mitophagy). The level of mitophagy and cardioprotective impact during ischemia and reperfusion remains elusive and demands further investigation. Objective: To assess mitophagy during ischemia-reperfusion simulation in human EHTs. Methods and results: A hiPSC line was genetically modified using CRISPR/Cas9 knock-in to insert a fluorescent tag (mCherry or EGFP) on Translocase of the Outer Mitochondrial Membrane 20 ( TOMM20) gene resulting in hiPSCs with fluorescent mitochondria. The hiPSCs were differentiated to cardiomyocytes that were embedded in a fibrin hydrogel between two flexible silicone posts to generate EHTs. The EHTs (21 days or older) were subjected to 90 min of ischemia simulation followed by 120 min of simulated reperfusion with and without the lysosomal inhibitor Bafilomycin A1 (BafA1) to measure flux. Time-matched control EHTs remained in normal conditions (with and without BafA1). The EHTs were fixed and sections were immunostained with the lysosomal marker LAMP1A and analyzed by confocal microscopy. Co-localization of fluorescent mitochondria and stained lysosomes was observed after 120 min of reperfusion. To further assess this co-localization we used proximity ligation assay (PLA), an antibody-based assay allowing verification of close proximity (within 40 nm) of two proteins resulting in a single fluorescent signal (PLA dot). We performed the assay using anti-TOMM20 and anti-LAMP1A antibodies to localize mitochondrial content within lysosomes. Notably, there was a significant increase in the number of PLA dots in response to 120 min of reperfusion in the presence of BafA1 (3.41±0.56 fold vs. control, p&lt;0.01; n=4), indicative of induced mitophagy flux. Conclusion: We observed a marked increase in lysosomal degradation of mitochondria in EHTs during reperfusion. The functional impact on EHTs during ischemia and reperfusion needs further research.
Abstract 14766: Development of an Ex-Vivo Vascular Bioreactor to Investigate Viability of Coronary Arteries
Authors: Francesca Razzi, Marco Stijnen, Dirk J Duncker, Volkert van Steijn, Heleen M Van Beusekom
Journal: Circulation (2022)

Introduction: The cardiovascular disease that causes most of the deaths is atherosclerosis. The current research to assess efficacy of treatments is based on animal models, but these present several limitations related to time and costs associated. Ex-vivo systems represent useful models to study vascular biology and to test medical devices. The main goal of this research was to culture coronary arteries in an ex-vivo vascular bioreactor in order to maintain them alive and functional by mimicking physiological conditions. Methods: Culture experiments were performed on porcine right coronary arteries (RCA). Duration was set to 2 (n=3), 4 (n=3), and 9 days (n=3). The RCAs were dissected from hearts harvested from a local slaughterhouse. The bioreactor containing the dissected RCA was placed in a 38°C incubator. The RCA was cultured in a blood-mimicking culture medium. To assess RCA morphology and diameter, ultrasound imaging was performed. Pressure and flow rate were monitored daily. The flow rate was set to ensure a physiological peak endothelial shear stress of around 0.8-1.8 Pa. After 2, 4 or 9 days of culture, the RCA was embedded in paraffin and cut into 4 μm sections. Histological stainings (H&amp;E and RF) were performed on the sections. Results: During RCA cultures, the mean pressure was 60-100 mmHg, and the peak flow rate was around 60 ml/min. Ultrasound imaging showed that the morphology and structure of cultured arteries was maintained during the culture. Histological analyses showed preserved endothelium and extracellular matrix. After 2 days of culture, endothelial coverage was not complete while after 4 days it was completely restored. After 9 days of culture, a layer of newly formed neointima was visible. Conclusions: The cultured RCAs maintained their physiological morphology up to 9 days of culture. The investigated model represents a useful tool for testing vascular therapies and devices, supporting the translational phase between in-vitro and in-vivo studies.
Abstract 15395: Caveolin-1 is a Primary Determinant of Endothelial Stiffening Associated With Dyslipidemia, Disturbed Flow and Ageing
Authors: Elizabeth Le Master, Victor Aguilar, Amit Paul, Dana Lazarko, Sang Joon Ahn, James Lee, Richard D Minshall, Irena Levitan
Journal: Circulation (2022)

Objective: Endothelial stiffness is emerging as a major determinant in endothelial function. Here, we analyzed the role of caveolin-1 (Cav-1) in determining the stiffness of endothelial cells exposed to oxidized low density lipoprotein (oxLDL) under static and hemodynamic conditions in vitro and of aortic endothelium in vivo in mouse models of dyslipidemia and ageing. Approach and Results: Elastic moduli of cultured endothelial cells and of endothelial monolayer of freshly isolated mouse aortas were measured using atomic force microscopy. We found that a loss of Cav-1 abrogates the uptake of oxLDL (n=5-8) and oxLDL-induced endothelial stiffening (n=4-5) but has no effect on endothelial stiffness in the absence of oxLDL (n=4). A loss of Cav-1 also abrogated endothelial stiffening induced by disturbed flow, which in turn is oxLDL dependent (n=6). Mechanistically, Cav-1 is required for the expression of CD36 (cluster of differentiation 36) scavenger receptor (n=4) but not for endothelial stiffening induced by a direct application of 7ketocholesterol (n=8). Genetic deletion of Cav-1 also led to profound changes in endothelial stiffness in vivo : it abrogated endothelial stiffening observed in the disturbed flow region of the aortic arch (n=5-6), abrogated endothelial stiffening induced by feeding the mice high fat diet (4-6 weeks, n=5) and significantly blunted endothelial stiffening that develops with advanced age (n=5-6). This effect was independent of stiffening of the sub-endothelium layer (n=5-8). Conclusions: Taken together, this study demonstrates that Cav-1 plays a critical role in endothelial stiffening induced by oxLDL in vitro and by dyslipidemia, disturbed flow and ageing in vivo . Mechanistically, Cav-1 regulates endothelial stiffening via CD36-mediated uptake of oxLDL, whereas exposure to 7ketocholesterol circumvents this step.
Abstract 14726: Serial Assessment of Cardiac Biomarkers and Risk of Cardiovascular Death or Hospitalization for Heart Failure in DECLARE-TIMI 58
Authors: David D Berg, Stephen D Wiviott, Itamar Raz, Petr Jarolim, Erica Goodrich, ofri Mosenzon, Avivit Cahn, Deepak Bhatt, Lawrence Leiter, Darren K McGuire, JOHN WILDING, Ingrid A Gause-nilsson, Marc S Sabatine, David A Morrow
Journal: Circulation (2022)

Introduction: Circulating cardiovascular (CV) biomarkers, including N-terminal pro-B type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT), are associated with risk of heart failure (HF) events in patients (pts) with type 2 diabetes (T2D). Less is known about the prognostic significance of changes in these biomarkers over time or the early effects of the SGLT2i dapagliflozin (dapa) on these markers. Methods: DECLARE-TIMI 58 was a randomized, placebo-controlled trial of dapa in 17,160 pts with T2D (median f/u = 4.2y). NT-proBNP &amp; hsTnT (Roche) were measured at baseline &amp; 6 mo. The outcome of interest was CV death (CVD) or hosp for HF (HHF). Outcome analyses were performed from a landmark of the 6-mo study visit with pts categorized by change in each biomarker over the first 6 mo. Hazard ratios were adjusted for baseline biomarker value, randomized treatment, age, sex, race, smoking, eGFR, prior HF, BMI, T2D duration, insulin use, CAD, prior MI, ischemic stroke, PAD, dyslipidemia, &amp; hypertension. Linear mixed models were used to assess the effect of dapa on log-transformed NT-proBNP &amp; hsTnT. Results: Serial NT-proBNP &amp; hsTnT values were available in 13,459 pts (78%). Among pts allocated to placebo (n=6,698), NT-proBNP was more dynamic than hsTnT (≥20% change from baseline in 71% vs. 33% of pts; p&lt;0.001). In the full cohort, independent of randomized treatment, there was a stepwise graded relationship between change in NT-proBNP &amp; hsTnT and risk of CVD/HHF, whereby increases in either biomarker were associated with higher risk and decreases in either biomarker were associated with lower risk (p-trend for adj-HR &lt;0.001 for each). Considered together, changes in the 2 markers were complementary ( Fig ; p&lt;0.001). Dapa significantly reduced NT-proBNP (relative LS mean change, -6% [-4% to -8%]; p&lt;0.001) but not hsTnT (0% [-1% to +1%]; p=0.92) over 6 mo. Conclusions: Early changes in hsTnT &amp; NT-proBNP are associated with subsequent risk of CVD/HHF in pts with T2D.
Abstract 14425: Improved Carcinoid Heart Disease Mortality Amid Persistent Race, Income, and Rural Disparities: Propensity Score and Machine Learning Guided Analysis of 55,910 Carcinoid Cases From 2016-2018
Authors: Dominique Monlezun, Saamir Hassan, Kevin Honan, Jin wan Kim, Daniel Halperin, Arvind Dasari, James Yao, Igor Gregoric, Mehmet Cilingiroglu, Konstantinos Marmagkiolis, Efstratios Koutroumpakis, Cezar Iliescu
Journal: Circulation (2022)

Introduction: It is unclear what the rates of carcinoid heart disease (CHD) diagnosis, disparities, and inpatient outcomes are. Methods: We performed the first nationally representative longitudinal analysis of the above using Machine Learning-augmented Propensity Score adjusted multivariable regression (ML-PSr) and the 2016-2018 National Inpatient Sample (NIS), the United States’ largest all-payer inpatient dataset. The propensity score was modified for the likelihood of developing malignant carcinoid tumor (MCT). Results: From 2016-2018 among 101,521,656 hospitalizations, 55,910 (0.05%) had a malignant carcinoid tumor (MCT), of whom 4,030 (7.20%) had CHD. The rate of CHD diagnosis remained largely stable from 2016 (18,900 [0.06%]) to 2017 (19,025 [0.05%]) to 2018 (17,985 [0.05%]). Patients with versus without CHD had significantly higher unadjusted mortality in 2016 (4.05% versus 2.19%), 2017 (3.75% versus 1.95%), and 2018 (3.75% versus 1.95%). Of patients with CHD, 0.15% had acute carcinoid syndrome. Compared to the racial distribution throughout the population, the diagnosis of CHD was under-represented in Hispanics (12.83% versus 7.95%), Asians (3.13% versus 2.84%), lowest income quartile (29.47% versus 28.07%), second lowest income quartile (26.90% versus 25.41%), metros of 250,000-999,999 residents (20.79% versus 19.73%) and metros of 50,000-249,999 (9.30% versus 8.56%) (all p&lt;0.001). In ML-PS multivariable regression fully adjusting for age, sex, race, metro density, region, metastasis, and NIS calculated mortality risk by DRG, CHD initially significantly increased mortality in 2016 (OR 1.18, 95%CI 1.10-1.28; p&lt;0001) but decreased it in 2017 (OR 0.76, 95%CI 0.70-0.82; p&lt;0.001) and 2018 (OR 0.78, 95%CI 0.72-0.84; p&lt;0.001). In ML-PSr stratified by income in 2018, there was largely a step wise decrease in mortality with CHD from the lowest income quartile to highest income quartile. Conclusions: Our analysis demonstrates that racial minorities, lower income, and more rural metros have lower rates of CHD diagnosis, its associated mortality appears to be the lowest with higher income, and its mortality over time across all patients in general appears to be decreasing potentially with improved inpatient care.